ITGAM-mediated macrophages contribute to basement membrane damage in diabetic nephropathy and atherosclerosis.

BACKGROUND: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive. METHODS: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues. RESULTS: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM. CONCLUSION: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications.

Family Aggregation of Hematological Malignancies Discovered from an Acute Myeloid Leukemia Patient with STK11 and THBD Gene Mutation.

Acute myeloid leukemia (AML) is a large class of heterogeneous hematological malignancies with the highest incidence rate in acute leukemia. Its pathogenesis is still unclear, which may be related to genetics. According to the latest AML NCCN guidelines, genes involved in AML family genetic changes include RUNX1, ANKRD26, CEBPA. Finding new genes related to AML genetics is of great significance for predicting the prognosis of patients, developing targeted drugs, and selecting transplant donors. Here, we report a case of adult female AML patient whose three relatives suffered from hematological malignancies, including Waldenstrom macroglobulinemia, NK/T-cell lymphoma, and angioimmunoblastic T-cell lymphoma. The screen for genetic susceptibility genes related to blood and immune system diseases was carried out, and the result showed that the patient herself, her son, her daughter, and her two cousins all had STK11 p.F354L and/or THBD p.D486Y mutations. At present, there is no research or case report on the relationship between STK11/THBD and family aggregation of hematological malignancies. We report for the first time that an AML patient with STK11 and THBD mutations has a family aggregation of hematological malignancies, and consider that STK11 and THBD may be related to family genetic changes which ultimately cause the family aggregation of hematological malignancies.

Incidence and Related Factors for Hospital-Acquired Pneumonia Among Older Bedridden Patients in China: A Hospital-Based Multicenter Registry Data Based Study.

Objective: To identify the incidence and related factors for hospital-acquired pneumonia (HAP) among older bedridden patients in China. Study design and setting: This multicenter registry data-based study conducted between November 2015 and March 2016 surveyed 7,324 older bedridden patients from 25 hospitals in China (six tertiary, 12 non-tertiary, and seven community hospitals). The occurrence of HAP among all participants was monitored by trained investigators. Demographics, hospitalization information and comorbidity differences were compared between patients with and without HAP. A multilevel regression analysis was used to explore the factors associated with HAP. Results: Among 7,324 older bedridden patients, 566 patients were diagnosed with HAP. The incidence of HAP in this study was 13.9 per 1,000 person-days. There were statistical differences in gender, age, length of bedridden days, BMI, smoking, department, undergoing general anesthesia surgery, ventilator application, Charlson comorbity index (CCI) score, disturbance of consciousness, tranquilizer use, glucocorticosteroid use, and antibiotic use between patients with HAP and patients without HAP (all p < 0.05). Multilevel regression analysis found no significant variance for HAP at the hospital level (0.332, t = 1.875, p > 0.05). There were significant differences for the occurrence of HAP among different departments (0.553, t = 4.320, p < 0.01). The incidence density of HAP was highest in the ICU (30.1‰) among the selected departments, followed by the departments of neurosurgery (18.7‰) and neurology medicine (16.6‰). Individual patient-level factors, including older age, disturbance of consciousness, total CCI score, ICU admission, and glucocorticoid and antibiotic use, were found to be associated with the occurrence of HAP (all p < 0.05). Conclusion: A relatively high incidence density of HAP among older bedridden patients was identified, as well as several factors associated with HAP among the population. This suggests that attention should be paid to the effective management of these related factors of older bedridden patients to reduce the occurrence of HAP.

Enhanced antitumor effect of combining chemotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes in mice with EBV-related non-Hodgkin's lymphoma.

Epstein-Barr virus (EBV)-related non-Hodgkin's lymphoma (NHL) represents a major problem in hematological clinical studies due to its drug tolerance and refractoriness. EBV infection is a key factor driving the process of tumor growth. Immune therapy is an important biotherapeutic method of treating cancer, which is attracting increasing attention. We hypothesized that combining conventional chemotherapy with immune therapy in the treatment of EBV-related NHL may achieve better outcomes. First, we successfully cloned large numbers of EBV-specific T cells by immune stimulation ex vivo. Subsequently, the combined therapy was applied in a murine model of human EBV-related NHL. As expected, combined therapy inhibited tumor growth more effectively compared with monotherapy. In addition, we continuously tested the tumor-associated immune microenvironment and observed that the numbers of tumor-infiltrating cytotoxic T lymphocytes (CTLs) and macrophages were elevated following combined therapy. These effects suggest that EBV-specific CTLs may indirectly promote an innate immune reaction in lymphoma by activating tumor-infiltrating macrophage proliferation. Our findings may provide a guide for the prospective treatment of EBV-related NHL.

Improving Breast Cancer Outcomes among Women in China: Practices, Knowledge, and Attitudes Related to Breast Cancer Screening.

Background. Breast cancer is a major public health issue and the most commonly diagnosed cancer for women worldwide. Despite lower incidence rates than those living in Western countries, breast cancer incidence among Chinese women has increased dramatically in the past 20 years. Nevertheless, there is a paucity of studies reporting the attitudes toward and practices of breast cancer screening among Chinese women. Methods. This cross-sectional study examined the practices, knowledge, and attitudes toward breast cancer screening (BCS) on a convenience sample of 400 Chinese women. Results. Among study participants, 75% of the women never had a mammogram and the top three barriers reported were low priority, feeling OK, and lack of awareness/knowledge toward breast cancer screening. The results from the logistic regression model showed increased self-efficacy; having performed monthly self-exams, and having had clinical breast exams in the past two years were significant correlates while demographic variables were not correlated with screening behaviors. Conclusion. The findings provide a foundation to better understand beliefs and practices of Chinese women toward BCS and highlight the critical need for general public, health professionals, and the health care system to work collaboratively toward improving the quality of breast cancer care in this population.